E. Bozi

Poikiloderma of Civatte: a clinical and epidemiological study.

Background  Although a common dermatosis, idiopathic poikiloderma of the face and neck has not been studied in depth for decades.

Erythema Multiforme following Vaccination for Human Papillomavirus

Erythema multiforme (EM) is an acute self-limited immune-mediated reaction manifested by target skin lesions with mucous membrane involvement. The most common causes are infections and drugs. Vaccinations have been reported as a triggering factor, and they may be a frequent cause of EM in childhood. A 19-year-old female developed several target lesions of the hands and feet 10 days after the second dose of human papillomavirus (HPV) vaccine. Clinico-histologically, a diagnosis of EM minor was made. Treatment with topical corticosteroids and oral antihistamines resulted in complete clearance of the rash. Four months later, she received the last booster dose of the vaccine. A few subtle lesions appeared and disappeared spontaneously after a few days. Gardasil® is a non-infectious vaccine, developed for the prevention of cervical cancer, precancerous genital lesions and genital warts. It delivers the major capsid (L1) protein of HPV types 6, 11, 16 and 18. Mild local reactions are the main adverse events. The only serious events are very rare cases of anaphylaxis. In our patient, the temporal relationship between the development of EM and the vaccination suggests that the HPV vaccine probably was the causal agent. This is the first published case of EM following HPV vaccination.

Biologic Agents and Alopecia Areata

hibited hair growth and EGF, TNFand IL-1 completely abrogated it. All these evidences are in favor of an autoimmune phenomenon occurring in AA, with the TNFappearing as a potent inhibitor of hair growth. In the last few years, several biologic agents acting on TNFor involving ICAM 1-LFA1 or CD2-LFA3 interactions have been considered as possible treatments for AA. Cases of AA have been described in which etanercept has been proven ineffective, or AA recurred during etanercept therapy for other disease [5] . Strober et al. [6] found that no hair regrowth occurred after treatment of AA with etanercept in 17 otherwise healthy patients. In addition, infliximab did not prevent AA development in a patient with no previous history of this disease [7] . Fabre and Dereure [8] reported worsening of AA in a patient receiving infliximab. Adalimumab is a fully humanized recombinant anti-TNFmonoclonal antibody which has been approved for rheumatoid arthritis, active ankylosing spondylitis, psoriatic arthritis and Crohn’s disease. To our knowledge, our patient is the third reported case of AA developing during adalimumab therapy. Pelivani et al. [9] described a case of AA universalis elicited after 6 months of adalimumab monotherapy in a patient with a longstanding history of psoriatic arthritis and psoriasis. Garcia Bartels et al. [10] published a case of AA universalis, occurring 4 months after adalimumab was added to a regimen of prednisone and leflunomide. In our patient, apart from the introduction of adalimumab, other factors, namely serious psychological stress, might have played an important part in eliciting AA. Our patient is the second reported case in which the introduction of adalimumab in a patient already under treatment with leflunomide was followed by AA development. Leflunomide is a new immunomodulatory drug that selectively acts on activated autoimmune lymphocytes by inhibiting dihydroorotate dehydrogenase, an enzyme required for de novo pyramidine synthesis. These 2 cases suggest that leflunomide has probably no prophylactic or therapeutic effect on AA. On the other hand, there is evidence suggesting that other biologic therapies that target T cells may represent an effective treatment modality for AA. Heffernan et al. [11] tried alefacept in 4 patients with AA. All 4 patients improved, indicating that alefacept may be effective. A case of AA successfully treated with efalizumab has been reported [12] , however subcutaneous injections of efalizumab did not seem to be effective in 62 patients with AA [13] . Furthermore, in one case of AA, efalizumab was proven ineffective [7] . In light of the suggested pathogenetic relationship of AA and TNF, it is noteworthy to report cases of AA that occurred and progressed during treatment with TNF-blocking agents. The understanding gained from this experience should redirect the therapeutic aims toward alternate interventions.

Eruptive Large Melanocytic Nevus in a Patient with Hereditary Epidermolysis bullosa simplex

Hereditary epidermolysis bullosa (HEB) is a group of genetically determined mechanobullous disorders characterized by blister formation following minor trauma. Unusual melanocytic lesions may be a rare feature of all major categories of HEB. We report a large melanocytic nevus, clinically simulating malignant melanoma, which developed at a site of healing blisters in an 8-year-old male with recessive generalized epidermolysis bullosa simplex (EBS). Histological findings were consistent with a compound nevus. This is the third reported case of an eruptive melanocytic nevus developing in EBS. Due to their unique features, it has been suggested that these nevi may represent a distinct variant, referred to as epidermolysis bullosa nevi. Despite the atypical picture, no malignant transformation of HEB nevi has been seen. Therefore, after histologic verification, regular long-term follow-up rather than radical surgery is recommended.

A randomized, double‐blind, vehicle‐controlled study of a preparation containing undecylenoyl phenylalanine 2% in the treatment of solar lentigines

Background.  Solar lentigines are common, benign, cosmetically disfiguring lesions. Available physical treatments are effective, but they are costly and carry risks of side‐effects.

Poikiloderma of Civatte: A Histopathological and Ultrastructural Study

Background: Poikiloderma of the face and neck (Civatte) has not been studied in depth for decades, especially as far as the histopathology is concerned. Material and Methods: We studied 50 consecutive patients with poikiloderma of Civatte (PC). Their evaluation included: history, physical examination, lesional skin biopsy and histological examination of sections stained with hematoxylin-eosin, PAS, Fontana-Masson, acid orcein Giemsa for elastic fibers and toluidine blue for mast cells. In 10 randomly selected subjects, a second skin biopsy was performed and specimens were examined under the electron microscope. Results: There were 34 females (68%) and 16 males. The mean age at diagnosis was 47.8 years for females and 61.7 years for males. Histological examination revealed an atrophic (62%), flattened (84%) epidermis with hyperkeratosis (92%) and occasional follicular plugging (34%). In some cases, mild hydropic degeneration of the basal cell layer was evident (46%). Melanin was irregularly distributed in the lower epidermis (94%), and melanophages were often present in the dermis (92%). The most prominent and constant feature (100%) was solar elastosis of the papillary dermis. The blood vessels were almost invariably dilated (96%) with a mild perivascular lymphohistiocytic infiltrate (78%), sometimes with plasmacytes (56%). At the ultrastructural level, the epidermis showed only minor changes. The dermoepidermal junction was intact. The most constant findings were swelling and disruption of the collagen fibers as well as focal degeneration of the collagen bundles. Occasionally, several vacuolar spaces were found just under the basal lamina. Melanin-laden macrophages scattered in the dermis were also detected. Conclusions: PC shows distinct histological and ultrustructural features, supporting the theory that it represents a separate entity. The histology of PC is characteristic but not pathognomonic. On this basis, the differential diagnosis from Riehl’s melanosis, poikiloderma atrophicans et vasculare and other acquired poikilodermas can be made. Ultrastructural findings were consistent with the histological findings. Changes of the dermal connective tissue (solar elastosis) predominated, providing morphological evidence for the role of ultraviolet radiation in the pathogenesis of PC.

Association of Behcet's disease with hematologic malignancies.

Her paternal uncle suffered with type 1 insulin-dependent diabetes. On examination, she had a guttate pattern of lesions on her forehead (Fig. 1), shoulder, and upper arms in a light-exposed distribution. On close inspection, the lesions were found to be white atrophic macules. On her right shoulder she had a white plaque which had an atrophic cigarette paper appearance (Fig. 2). There was no anogenital involvement. A clinical diagnosis of lichen sclerosus was made, which appeared to be precipitated and aggravated by episodes of sunburn. A biopsy was taken which revealed epidermal atrophy, hyalinization of collagen in the upper dermis, and a scattered, deeper, predominantly lymphocytic infiltrate, consistent with a diagnosis of lichen sclerosus. Her routine investigations revealed that she was antinuclear antibody positive (1 : 80). Lichen sclerosus is much less common in children than in adults, and in only approximately 5% of cases are lesions seen solely outside the anogenital area. The cause of lichen sclerosus is unknown, but an autoimmune process has been proposed as there is a well-recognized association with other autoimmune diseases in patients and their relatives. It usually appears spontaneously, but there have been several reports of lichen sclerosus being precipitated by trauma. For example, lichen sclerosus has been described in an old burn scar, in a longstanding pressure sore, and following radiation therapy. To our knowledge, it has only once before been reported following sunburn. In that case, the patient was an adult male who also had genital involvement. This case represents another example of lichen sclerosus exhibiting the Koebner phenomenon.

A double‐blind vehicle‐controlled study of a preparation containing undecylenoyl phenylalanine 2% in the treatment of melasma in females

Undecylenoyl phenylalanine is a novel skin‐lightening agent, probably acting as α‐melanocyte‐stimulating hormone (α‐MSH) and beta‐adrenergic receptor (β‐ADR) antagonist.

Idiopathic bullous eosinophilic cellulitis (Wells' syndrome).

Wells syndrome (WS) is an uncommon inflammatory skin condition originally described by Wells in 1971 and renamed eosinophilic cellulitis in 1979. Although a wide variation in clinical presentation has been observed, vesiculobullous lesions are very rare. The aetiopathogenesis of WS is largely unknown. It seems to be a nonspecific hypersensitivity reaction to exogenous or endogenous stimuli, such as arthropod bites, infections or infestations, drugs, immunization or underlying internal disorders. Most importantly, WS has been associated with haematological malignancies, especially myeloproliferative or lymphoproliferative diseases and leukaemia. It can occur in association with Churg–Strauss syndrome (CSS) and hypereosinophilic syndrome, supporting the hypothesis that all these conditions belong to the same nosological spectrum. A 64-year-old Greek woman presented with a mildly pruritic, vesiculobullous eruption localized to the nape of the neck. The same eruption had been recurring at the same site for the past 3 years, about once every 2 months. The patient s personal and family history was unremarkable, except for uterine fibromyomas and osteoporosis; for the latter, she was taking alendronic acid and calcitriol. On physical examination, an oedematous and erythematous plaque, 100 mm in diameter, was seen on the right posterior side of the neck, on top of which vesicles containing clear fluid coalesced in some areas to form small bullae (Fig. 1a). Laboratory investigation revealed blood eosinophilia (0.7 · 10 ⁄ L; normal range 0.04–0.7 · 10 ⁄ L). Results of tests for faecal parasites and antibodies to serum herpes simplex virus types 1 and 2, patch testing with the standard series and with hair products used by the patient, and chest radiography and abdominal computed tomography were all negative. Histology showed a moderate oedema of the dermis and epidermis, and a lymphomonocytic inflammatory infiltrate with a large number of eosinophils and few neutrophils (Fig. 1b). No flame figures or signs of vasculitis were seen. Direct immunofluoresence of perilesional skin was negative for IgG, IgA, IgM and C3. (a)

Frontal Fibrosing Alopecia and Vitiligo: Coexistence or True Association

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia characterized by a progressive band-like recession of the frontotemporal hairline and frequent loss of the eyebrows. It predominantly affects postmenopausal women. Coexistence of FFA and vitiligo is rarely reported in the literature. We retrospectively studied 20 cases diagnosed with FFA in a 14-month period in our Department. Among them, there were 2 cases, a 72-year-old woman and a 48-year-old man, who developed FFA on preexisting vitiligo of the forehead. Anatomical colocalization of the two dermatoses supports the notion that a causal link may exist and their association may not be coincidental. We suggest that interrelated immunologic events and pathologic processes may underlie both these skin conditions.